The OMIM epileptic encephalopathy genes – a 2014 review

EIEE1-19. Online Mendelian Inheritance in Man (OMIM) is one of the most frequently accessed online databases for information on genetic disorders. Genes for epileptic encephalopathies are organized within a phenotypic series entitled Early Infantile Epileptic Encephalopathy (EIEE). The EIEE phenotypic series currently lists 19 genes (EIEE1-19). Let’s review the evidence for these genes as of 2014. Continue reading

Mutation intolerance – why some genes withstand mutations and others don’t

The river of genetic variants. The era of high-throughput sequencing has given us several unexpected insights into the human genome. One of these insights is the observation that mutations or variations can occur in parts of our genome without any major consequences. Every individual is a “knockout” for at least two genes in the human genome. This means that in every individual, both copies of a single gene are disrupted through mutations or small deletions or duplications. In addition, there are dozens, if not hundreds, of genes with disruptive mutations that affect only a single copy of the gene. Similar mutations in specific disease-associated genes, however, will invariably result in an early onset genetic disorder. This comparison already shows that the genes in the human genome differ with respect to the amount of disruptive genetic variation they can tolerate. A recent study in PLOS Genetics now tries to catalogue the genes in the human genome by assessing their mutation intolerance based on the genetic variation seen in large-scale exome datasets. Many genes for neurodevelopmental disorders are highly intolerant to mutations. Furthermore, some genes for monogenic epilepsies show surprising results in this assessment. Continue reading

Missed SCN1A mutations in Dravet Syndrome – a matter of degrees

Back from AES. I have just come back from the 66th Annual Meeting of the American Epilepsy Society and I would like to share some of the most recent findings that were presented at this meeting. Since we felt that our presentation on the “re-discovery” of SCN1A mutations in SCN1A-negative patients with Dravet Syndrome received quite some attention, I thought that I would share this part of our presentation as a brief screencast. In particular, I would like to thank Anna-Kaisa Anttonen and Anna-Elina Lehesjoki for providing us with the trace files. And of course thanks to everybody in RES who was involved in this.